Analog-based drug design concepts MCQs With Answer

Introduction: Analog-based drug design concepts MCQs With Answer equips B. Pharm students with practical knowledge of medicinal chemistry strategies used to optimize leads. This introduction covers core keywords: analog design, structure–activity relationship (SAR), bioisosteres, scaffold hopping, lead optimization, QSAR, pharmacophore modeling, ADMET, metabolic stability, and conformational restriction. You will learn how small structural changes—homologation, substituent modification, stereochemistry, ring replacement, or linker tuning—affect potency, selectivity, solubility, and safety. These focused MCQs emphasize real design decisions, trade-offs, and molecular rationales to deepen understanding of analog strategies and prepare you for applied drug discovery tasks. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary goal of analog-based drug design?

• To synthesize as many compounds as possible
• To improve the properties of a lead compound by modifying its structure
• To identify natural products only
• To replace clinical trials

Correct Answer: To improve the properties of a lead compound by modifying its structure

Q2. Which term best defines replacement of an atom or group with another that preserves biological activity?

• Homologation
• Bioisosterism
• Scaffold hopping
• Prodrugging

Correct Answer: Bioisosterism

Q3. What does scaffold hopping involve?

• Changing the core framework while retaining key pharmacophore features
• Adding polar groups to improve solubility
• Converting a drug into a prodrug
• Only modifying side chains without changing the core

Correct Answer: Changing the core framework while retaining key pharmacophore features

Q4. Homologation in medicinal chemistry refers to:

• Replacing a ring with a heterocycle
• Systematic addition or removal of methylene units in a chain
• Changing chirality at a stereocenter
• Attaching polyethylene glycol chains

Correct Answer: Systematic addition or removal of methylene units in a chain

Q5. Conformational restriction is used primarily to:

• Increase molecular weight
• Lock a molecule into a bioactive conformation to improve potency and selectivity
• Decrease polarity only
• Enhance oral absorption by adding flexible linkers

Correct Answer: Lock a molecule into a bioactive conformation to improve potency and selectivity

Q6. Structure–activity relationship (SAR) studies help to:

• Predict clinical trial outcomes without experiments
• Correlate chemical modifications with changes in biological activity
• Replace ADMET testing
• Only determine compound solubility

Correct Answer: Correlate chemical modifications with changes in biological activity

Q7. QSAR models are mainly used to:

• Determine synthetic feasibility
• Quantitatively relate molecular descriptors to biological activity
• Measure in vivo clearance directly
• Replace target identification studies

Correct Answer: Quantitatively relate molecular descriptors to biological activity

Q8. During lead optimization, which property is usually balanced against potency?

• Color of the compound
• ADMET (absorption, distribution, metabolism, excretion, toxicity) properties
• Marketing strategy
• Number of stereocenters only

Correct Answer: ADMET (absorption, distribution, metabolism, excretion, toxicity) properties

Q9. Increasing lipophilicity (LogP) of an analog commonly leads to:

• Decreased membrane permeability
• Increased aqueous solubility
• Higher membrane permeability and often higher metabolic clearance or toxicity
• Guaranteed improved oral bioavailability

Correct Answer: Higher membrane permeability and often higher metabolic clearance or toxicity

Q10. Why is pKa important in analog design?

• It determines the melting point only
• It influences the ionization state, which affects permeability and target binding
• It only affects color of the drug
• It is irrelevant for ADMET properties

Correct Answer: It influences the ionization state, which affects permeability and target binding

Q11. Introducing fluorine atoms to a metabolically labile position often:

• Increases metabolic stability by blocking oxidative metabolism
• Eliminates the need for toxicity testing
• Always makes the compound inactive
• Decreases binding affinity to all targets

Correct Answer: Increases metabolic stability by blocking oxidative metabolism

Q12. The main purpose of designing a prodrug analog is to:

• Directly increase in vitro potency
• Improve delivery, solubility, permeability or targeting and then be converted to the active drug in vivo
• Make the compound more chemically reactive
• Avoid patent issues only

Correct Answer: Improve delivery, solubility, permeability or targeting and then be converted to the active drug in vivo

Q13. How does stereochemistry often affect analog activity?

• Stereochemistry has no effect on biological activity
• Different stereoisomers can show large differences in potency, selectivity and metabolism
• All stereoisomers are metabolized equally
• Stereochemistry only affects color

Correct Answer: Different stereoisomers can show large differences in potency, selectivity and metabolism

Q14. Matched molecular pair analysis helps designers to:

• Compare experimental effects of small, single-point changes between pairs of analogs
• Design peptides only
• Predict crystal packing
• Automate synthesis without testing

Correct Answer: Compare experimental effects of small, single-point changes between pairs of analogs

Q15. An activity cliff describes:

• A steep drop in solubility with no potency change
• Two similar molecules with large differences in potency
• A sudden change in color of a compound
• An increase in melting point upon modification

Correct Answer: Two similar molecules with large differences in potency

Q16. Replacing a phenyl ring with a heterocycle in an analog is commonly done to:

• Increase molecular weight only
• Modulate hydrogen-bonding, polarity, and metabolic profile
• Make the molecule fluorescent
• Eliminate all lipophilicity

Correct Answer: Modulate hydrogen-bonding, polarity, and metabolic profile

Q17. A successful bioisosteric replacement is expected to:

• Always increase potency regardless of context
• Maintain or improve target interaction while altering physicochemical or ADMET properties
• Only change the synthetic cost
• Make compounds more toxic intentionally

Correct Answer: Maintain or improve target interaction while altering physicochemical or ADMET properties

Q18. Cyclization of a flexible side chain to a ring commonly improves:

• Conformational entropy costs and often increases potency and selectivity
• Only water solubility
• Number of hydrogen bond donors
• Degree of ionization

Correct Answer: Conformational entropy costs and often increases potency and selectivity

Q19. PEGylation of an analog is primarily used to:

• Increase hydrophobicity
• Improve solubility, circulation time, and reduce immunogenicity for biologics
• Make a compound more easily crystallizable
• Decrease molecular size

Correct Answer: Improve solubility, circulation time, and reduce immunogenicity for biologics

Q20. According to Hammett principles, electron-withdrawing substituents on an aromatic ring typically:

• Have no electronic effect
• Can lower basicity of nearby amines and influence binding and metabolism
• Always increase molecule flexibility
• Convert an acid into a base

Correct Answer: Can lower basicity of nearby amines and influence binding and metabolism

Q21. A pharmacophore model represents:

• The three-dimensional arrangement of features required for molecular recognition by a biological target
• The synthesis route for a drug molecule
• Only the toxicophores of a compound
• The melting behavior of a molecule

Correct Answer: The three-dimensional arrangement of features required for molecular recognition by a biological target

Q22. A “me-too” drug differs from “lead hopping” in that me-too drugs:

• Are novel chemotypes unrelated to known drugs
• Are structurally similar to existing drugs aiming for improved properties or market share
• Always have better safety profiles
• Are only developed for veterinary use

Correct Answer: Are structurally similar to existing drugs aiming for improved properties or market share

Q23. Which ADMET parameter is directly influenced by polar surface area (PSA)?

• Color
• Permeability and oral absorption
• Only melting point
• Protein synthesis rate

Correct Answer: Permeability and oral absorption

Q24. Why is synthetic feasibility considered during analog selection?

• Because only complex molecules are desirable
• To ensure analogs can be made at scale with reasonable cost and time
• To avoid biological testing
• To guarantee patentability

Correct Answer: To ensure analogs can be made at scale with reasonable cost and time

Q25. Deuterium substitution at metabolically vulnerable sites is used to:

• Completely stop metabolism
• Slow metabolic oxidation and potentially improve PK without changing potency significantly
• Increase the pKa dramatically
• Make compounds radioactive

Correct Answer: Slow metabolic oxidation and potentially improve PK without changing potency significantly

Q26. High topological polar surface area (TPSA) of an analog generally correlates with:

• Increased passive membrane permeability
• Poor passive oral absorption and reduced brain penetration
• Higher lipophilicity
• Faster metabolic clearance always

Correct Answer: Poor passive oral absorption and reduced brain penetration

Q27. Changing linker length in a bivalent or bifunctional analog affects:

• Only the compound’s color
• Spatial arrangement for dual binding and overall potency/selectivity
• The atomic number of elements
• Only solubility with no effect on binding

Correct Answer: Spatial arrangement for dual binding and overall potency/selectivity

Q28. Introducing heteroatoms into a ring system in analog design can:

• Modify hydrogen-bonding, polarity, and electronic distribution to tune interactions
• Make the ring completely inert to metabolism
• Ensure the compound is always basic
• Decrease synthetic accessibility in every case

Correct Answer: Modify hydrogen-bonding, polarity, and electronic distribution to tune interactions

Q29. Which strategy can reduce clearance caused by cytochrome P450 metabolism?

• Increase the number of rotatable bonds
• Introduce steric hindrance or replace labile hydrogen atoms with fluorine or deuterium
• Always increase lipophilicity without limit
• Remove all polar groups

Correct Answer: Introduce steric hindrance or replace labile hydrogen atoms with fluorine or deuterium

Q30. When selecting an analog for preclinical development, the most important balanced criteria include:

• Only lowest molecular weight
• Potency, selectivity, acceptable ADME profile, safety margins and synthetic feasibility
• Largest possible number of chiral centers
• Only the best patentability irrespective of toxicity

Correct Answer: Potency, selectivity, acceptable ADME profile, safety margins and synthetic feasibility

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